NM_020753.5:c.3262G>A

Variant names:

• chr17-75501812-C-T
• rs142355604
• NM_020753.5:c.3262G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020753.5(CASKIN2):​c.3262G>A​(p.Ala1088Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,546,296 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000080 (1 hom.)
• Consequence: CASKIN2 NM_020753.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.44
• Publications: 1 publications found

Genes affected

CASKIN2 (HGNC:18200): (CASK interacting protein 2) This gene encodes a large protein that contains six ankyrin repeats, as well as a Src homology 3 (SH3) domain and two sterile alpha motif (SAM) domains, which may be involved in protein-protein interactions. The C-terminal portion of this protein is proline-rich and contains a conserved region. A related protein interacts with calcium/calmodulin-dependent serine protein kinase (CASK). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008876979).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020753.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASKIN2	NM_020753.5	MANE Select	c.3262G>A	p.Ala1088Thr	missense	Exon 18 of 20	NP_065804.2	Q8WXE0-1
	CASKIN2	NM_001142643.3		c.3016G>A	p.Ala1006Thr	missense	Exon 17 of 19	NP_001136115.1	Q8WXE0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASKIN2	ENST00000321617.8	TSL:1 MANE Select	c.3262G>A	p.Ala1088Thr	missense	Exon 18 of 20	ENSP00000325355.3	Q8WXE0-1
	CASKIN2	ENST00000861913.1		c.3325G>A	p.Ala1109Thr	missense	Exon 18 of 20	ENSP00000531972.1
	CASKIN2	ENST00000861914.1		c.3325G>A	p.Ala1109Thr	missense	Exon 18 of 20	ENSP00000531973.1

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 68 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000177 AC: 34 AN: 191888 AF XY: 0.000108

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.000268

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000781

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000803 AC: 112 AN: 1394004 Hom.: 1 Cov.: 51 AF XY: 0.0000801 AC XY: 55 AN XY: 686750

African (AFR) AF: 0.000795 AC: 25 AN: 31428

American (AMR) AF: 0.000198 AC: 7 AN: 35290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21260

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39240

South Asian (SAS) AF: 0.0000135 AC: 1 AN: 74050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5396

European-Non Finnish (NFE) AF: 0.0000685 AC: 74 AN: 1080962

Other (OTH) AF: 0.0000174 AC: 1 AN: 57458

GnomAD4 genome AF: 0.000447 AC: 68 AN: 152292 Hom.: 0 Cov.: 33 AF XY: 0.000457 AC XY: 34 AN XY: 74476

African (AFR) AF: 0.00135 AC: 56 AN: 41556

American (AMR) AF: 0.000131 AC: 2 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000362 Hom.: 0

Bravo AF: 0.000378

ESP6500AA AF: 0.000684 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000174 AC: 21

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.18
DANN	Benign	0.73
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.0089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		-1.4
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.026
Sift	Benign	0.56	T
Sift4G	Benign	0.46	T
Polyphen		0.0010	B
Vest4		0.044
MVP		0.26
MPC		0.13
ClinPred		0.0037	T
GERP RS		-6.9
Varity_R		0.035
gMVP		0.089
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs142355604; hg19: chr17-73497893; COSMIC: COSV58597501; COSMIC: COSV58597501;